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Studies have demonstrated that at least 20% of individuals infected with SARS-CoV-2 remain asymptomatic1–4. Although most global efforts have focused on severe illness in COVID-19, examining asymptomatic infection provides a unique opportunity to consider early immunological features that promote rapid viral clearance. Here, postulating that variation in the human leukocyte antigen (HLA) loci may underly processes mediating asymptomatic infection, we enrolled 29,947 individuals, for whom high-resolution HLAgenotyping data were available, in a smartphone-based study designed to track COVID-19 symptoms and outcomes. Our discovery cohort (n= 1,428) comprised unvaccinated individuals who reported a positive test result for SARS-CoV-2. We tested for association of five HLAloci with disease course and identified a strong association between HLA-B*15:01and asymptomatic infection, observed in two independent cohorts. Suggesting that this genetic association is due to pre-existing T cell immunity, we show that T cells from pre-pandemic samples from individuals carrying HLA-B*15:01were reactive to the immunodominant SARS-CoV-2 S-derived peptide NQKLIANQF. The majority of the reactive T cells displayed a memory phenotype, were highly polyfunctional and were cross-reactive to a peptide derived from seasonal coronaviruses. The crystal structure of HLA-B*15:01–peptide complexes demonstrates that the peptides NQKLIANQF and NQKLIANAF (from OC43-CoV and HKU1-CoV) share a similar ability to be stabilized and presented by HLA-B*15:01. Finally, we show that the structural similarity of the peptides underpins T cell cross-reactivity of high-affinity public T cell receptors, providing the molecular basis for HLA-B*15:01-mediated pre-existing immunity.

A computer program has been designed to simulate the process by which humans recognize the syntactic structure of sentences.

THE object of the communications on the liquefaction of gases, which have recently appeared in NATURE and the Philosophical Magazine, is to depreciate; the work of Cailletet and Pictet, to smother away the first-class work of the deceased Wroblewski 5 to annihilate myself, and thereby to magnify the claims for originality of Prof. Olszewski. In spite of the mistakes inevitable to pioneers, the work of Cailletet and Pictet must always be credited with originating research in this department. To show my appreciation of such investigation, and to give it a wide publicity in the year 1878, a Friday evening address was devoted to the work of Cailletet and Pictet, during the course of which I showed for the first time in this country the working of the Cailletet apparatus. Similarly, in the year 1884, an address was given on the work of Wroblewski and Olszewski, in the course of which I illustrated for the first time in public the liquefaction of oxygen and air, showing the boiling point, &c, by means of a simple form of apparatus which did not involve the use of the Cailletet pump as employed by these experimenters. To deliver a lecture on the work of other people is generally considered a mark of honour, and as usefully diffusing a knowledge of the same. The critic has for some object omitted half the opening sentence of this address, which runs as follows:—

THE existence of a new type of aromatic ring system, tropolone (I), was first postulated1to account for the chemistry of stipitatic acid, and the occurrence of this ring system in a variety of natural products has now been established2. Various derivatives of tropolone have been synthesized3, and recently three independent syntheses of tropolone have been described4. Since it is evident that its chemistry will soon be investigated in detail, it seems of interest to see whether its behaviour can be predicted theoretically before such experimental evidence is at hand.

IN a general survey of the polymerization of vinyl compounds using the method previously described1, we have studied methyl methacrylate, and have found that it presents features of some interest.

THERE is increasing evidence that nervous activity and brain RNA metabolism are closely related1–5. The present investigations were instigated to obtain further evidence for a connexion between RNA turnover and nervous activity in the visual cortex. We wished to accomplish this without recourse to electrical, chemical or any other form of non-physiological stimulation, and were fortunate in having available two strains of rats which seemed to be ideal preparations for this purpose.

Birkinshaw, Chambers and Raistrick1have described stipitatic acid, a metabolite of the mould Penicillium stipitatum, to which, after lengthy examination, they could ascribe no reasonable structure. The evidence they give, however, does seem to indicate a unique structure for the compound. The evidence is as follows:

THE Ni(II) complex of the macrocycle ligand I (CR) can be reduced catalytically with hydrogen to the system shown in II (reduced ligand, CRH)1. We were interested in determining the structure of this reduced nickel macrocycle because of the various possible isomers that can exist for the reduced macrocycle. The isomers originate from both the positions of the methyl groups arid the positions of the three hydrogens of the NH system. The various isomers are stable species because the lone pairs of the nitrogen atoms are used in bonding with the nickel atom. The fourteen possible geometric isomers of Ni(CRH)2+are schematically shown in Fig. 1.

HIGMAN1recently suggested a new mechanism for the Beckmann rearrangement which postulates that the cation (I) rearranges by rotation of the central > C = N < unit through 90° to form (II). This suggestion, though ingenious, is not in accordance with the known facts.

THROUGH the kindness of Dr. A. P. Orr of the Marine Station, Millport, in supplying a quantity of Gigartina stellata which is used in the preparation of ‘British Agar’1, we have been able to investigate a polysaccharide isolated from this material.

IN view of the remarkable physiological properties of colchicine its chemical nature is of some interest. Until recently, the structure (I) proposed by Windaus1has been generally accepted, although the stability of colchicine did not suggest a 9-amino-9: 10-di-hydrophenanthrene system, and although the salicylaldehyde enol structure of ring C appeared fantastic. Cohen, Cook and Roe2have now provided evidence that ring B must be 7-membered, but the exact location of the acetamido group remains uncertain; the isolation by Windaus of 4-methoxyphthalimide from the oxidation product of acetylcolchinol methyl ether suggested that the group was adjacent to ring C, but Lettré and Fernholz3have found that only β-anisylethylamine derivatives act as mitosis poisons.

IN a long letter which you published in NATURE of February 14, Mr. Pattison Muir charged me with appropriating the work of Olszewski and passing it off as my own. I replied at some length, riot on account of the intrinsic importance of the attack, but because there are always persons ready to assume? hat a charge of this kind, by whomsoever made, must be unanswerable unless it is answered. But as I can conceive nothing more unintere ting to your readers or myself, than a mere dialectical controversy with Mr. Muir, my reply to his letter published on the 21st will be brief.

MANY years ago, on recovering consciousness twelve hours after a railway accident in which my jaw was broken, I saw everything double in this position :—

THE main features of the autoxidation of unsaturated hydrocarbons have been established by Bolland and Gee1. The autoxidation of tetralin probably follows a similar course, although the published work2is open to criticism. If the kinetic scheme of Bolland and Gee is accepted, dye photosensitization offers a convenient method of determining the velocity constants absolutely. In our programme of work on absolute velocity constants3, we have therefore studied the sensitized oxidation of tetralin.

IT is well known that cellulose fabrics dyed with certain vat dyes disintegrate on exposure to light1. The experimental evidence suggests that a photosensitized oxidation of the cellulose is responsible. It is known that dyes do, in fact, photosensitize a number of reactions2; but no systematic survey of the field has been attempted, and the factors which determine the relative efficiencies of different dyes are not known. In a preliminary study of photosensitization, we have found that such dyes can initiate the autoxidation of tetralin, and the polymerization of styrene.

MR. HAMPSON seems insatiable of contradictions. He has produced a vast quantity of irrelevancies with which I have no concern. But I have denied the accusations he brings against me, and every single statement of his that is relevant. Yet he still complains that I do not deny enough. It is absolutely false to say that I appropriated or profited by any plan, idea, or statement of Mr. Hampson's, either directly or indirectly. I was never informed of his visit, far less of any of the plans he brought to the Royal Institution, nor would anything have induced me to look at them. I have been long enough in this “temple of science” not to know what that might involve. Mr. Hampson got at my assistant behind my back, and persuaded him to look at the plans. I infer from the public correspondence, that he saw that they would not work, and he told Mr. Hampson why they were unworkable.

PROF. SCHUSTER in his last communication on “The Spectrum of Metargon” says, “taking the spectroscopic evidence by itself, it points in the direction that the gas under examination is a compound of carbon either with argon or with a so far unknown body.”

THE attention of writers on Applied Mechanics should be called to the error continuously repeated in about thirty editions of the late Prof. Rankine's different works which have appeared during the last thirty years. The error is stilt reproduced in quite recent works of other writers : Prof. Ewing's article, “Steam-Engine,” in the Encyclopædia Britannica; Prof. Unwin's “Elements of Machine Design”; Prof. Alexander's “Elementary Applied Mechanics”; &c.

THE accepted mechanism for the polymerization of vinyl compounds involves four velocity constants: initiation (k1), chain propagation (k2), chain transfer (k3), and termination (k4). It is well known that standard methods of investigation give only two relations for the determination of these coefficients. In the absence of any transfer reaction, these relations determine k1and one of the ratios k2/k4, k2/k41/2.according to the order of the termination reaction. Melville1has recently described a method which provides another relation between the velocity constants, and hence allows their absolute values to be calculated under conditions such that transfer is unimportant.

Two electronic theories have been proposed for the benzidine rearrangement1,2, but both are open to criticism. The present theory is an elaboration of the Robinson2mechanism in terms of the quantum theory3of aromatic structure.

SOME time ago1Paranjape, Phalnikar, Bhide and Nargund reported a synthesis of santonin from optically inactive materials: they now2claim that their product was active, beingalmost entirely the natural (l-) isomer. They state that the activity, originated in the methylation of a 2-formylcyclo-hexanone derivative, and that the crude methylation product from 2-formylcyclohexanone (I) itself had the large specific rotation of −26.2° in chloroform. Although they did not isolate 2-methyl-2-formyl-cyclohexanone (II), they claim that an optically active derivativewas prepared in a state of purity.

MY communication on this subject was written in ignorance of the work of Barton, Cook and Loudon, which was partly disclosed at a meeting of the Chemical Society, but is still unpublished. In relation to the facts known when I wrote, my remarks on the nature of ring B in colchicine can scarcely be described as unduly speculative. In any event I reserve any possible discussion for the time when all the facts are available. This question of the structure of ring B is, of course, important, but it can be settled by application of routine methods of alkaloid chemistry. On the other hand, the suggestion I have ventured to make regarding ring G is quite novel in this field.

BROSS1claims that our article on the recognition of syntactic structure by computer2is refuted by its first sentence. Had he read the rest of the article with equal care he would have seen that this is not the case.

IT has been found that the electrical conductivity of a flame burning a mixture of hydrogen and nitrogen (in air) is very sensitively affected by the vapours of organic substances, and this effect can be used for detection purposes in gas chromatography.

THE glass strip collector for column chromatography to be described presents a visible result of an analysis in a manner similar to one-dimensional paper chromatography, but without the need for specific development reagents. Fractions can be isolated and estimated quantitatively.

I HAVE read the letter of Charles Olszewski, and but for your courtesy in drawing my attention to it would have allowed it to pass without notice. Considering the Royal Society, in the year 1878, awarded the Davy medal to Cailletet and Pictet for their achievements of the liquefaction of the so-called permanent gases, it is hardly likely I could put forward in England any claim for such a result. A reference to the Proceedingsof the Royal Institution between the years 1878 and 1893 will be sufficient to remove the suggestion that the apparatus I use has been copied from the Cracovie Bulletinof 1890. The work of the late Prof. Wróblewski has been fully acknowledged in England, and I am not aware of any injustice done to Charles Olszewski on account of the alleged omission of his subsequent investigations from public notice.

THE frequency factors and activation energies for reactions in the polymerization of styrene and vinyl acetate have been determined in these Laboratories1. By combining the values for chain propagation with the results of Lewis, Mayo, Walling and their collaborators2, activation energies and frequency factors can be calculated for a number of transfer and propagation reactions of the styryl radical. The accompanying diagram is a plot of E against log10A for the twenty-nine reactions. It will be seen that the frequency factors are in general low, the mean value of log10A being 7.4, instead of the normal value c. 12. As Gregg and Mayo2point out, there is, however, a tendency for reactions with high activation energies to have higher frequency factors.